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. 2020 Feb 10;21(1):48.
doi: 10.1186/s12931-020-1315-4.

Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry

Colin H Holtze  1 , Elizabeth A Freiheit  2 , Susan L Limb  3 , John L Stauffer  3 , Karina Raimundo  3 , Wayne T Pan  3   4 , Kevin R Flaherty  5 , Hyun J Kim  6
Affiliations

Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry

Colin H Holtze et al. Respir Res. .

Abstract

Background: Pragmatic use of the anti-fibrotic medications pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) in the United States (US) has not been studied and may be different from international settings due to structural differences between health care systems. This study examined the relationship between patient- and site-level characteristics and anti-fibrotic (a) use and (b) selection.

Methods: Data from the Pulmonary Fibrosis Foundation Patient Registry was used to perform univariable and multivariable regressions with generalized linear mixed models. A random effects model examined registry site variation.

Results: 703 of 1218 (57.7%) patients were taking a single anti-fibrotic of which 312 (44.4%) were taking nintedanib and 391 (55.6%) were taking pirfenidone. Up to 25% of patients using an anti-fibrotic may have been excluded from clinical trial participation due to having too severe disease as measured by diffusion limitation for carbon monoxide. Age (OR = 0.974, p = 0.0086) and diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 0.896, p = 0.0007) was negatively associated with anti-fibrotic use while time (in log of days) since diagnosis (OR = 1.138, p < 0.0001), recent patient clinical trial participation (OR = 1.569, p = 0.0433) and oxygen use (OR = 1.604, p = 0.0027) was positively associated with anti-fibrotic use. Time (log of days) since diagnosis (OR = 1.075, p = 0.0477), history of coronary artery disease (OR = 1.796, p = 0.0030), presence of pulmonary hypertension (OR = 2.139, p = 0.0376), patient clinical trial participation in the prior 12 months (OR = 2.485, p = 0.0002), diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 1.138, p = 0.0184), anticoagulant use (OR = 2.507, p = 0.0028), and enrollment at a registry site in the Midwest region (OR = 1.600, p = 0.0446) were associated with pirfenidone use. Anti-fibrotic use varied by registry site. Rates of discontinuation were modest and nearly identical for the two medications with side effects being the most common reason given for discontinuation. Twenty-three percent (23%, 274) of persons with IPF were using or had recently used an immunomodulatory agent.

Conclusions: This analysis provides a detailed characterization of IPF treatment patterns in the US; many users of anti-fibrotic medications may not have qualified for inclusion in clinical trials. More research is needed to understand variations in medical decision-making for use and selection of anti-fibrotic medication.

Keywords: Clinical decision-making; Idiopathic pulmonary fibrosis; Therapeutics.

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Conflict of interest statement

CH is supported by NIH Grant No. T32 HL007749–26. EF is a managing director of the SABER unit within the department of biostatistics at the University of Michigan. SABER receives funding from the Pulmonary Fibrosis Foundation. JS, SL and KR are employees of Genentech. WP is a former employee of Genentech. He is currently employed at BioMarin. KF reports personal fees from Veracyte and Sanofi Genzyme; and grants and personal fees from Roche/Genentech and Boehringer Ingelheim, outside of the submitted work. HK has served as site principle investigator for IPF clinical trials sponsored by InterMune, Gilead, Sanofi, Celgene, and Centocor.

Figures

Fig. 1
Fig. 1
Random Effects Model for Anti-fibrotic Prescription with Patient and Registry Site Variables by Registry Site. In the random effects model for any anti-fibrotic prescription using registry site as a random intercept, there was evidence for variation in propensity to prescribe anti-fibrotics between registry sites after accounting for differences in patient and site characteristics. The IOR-80 (80% interval odds ratio) crossed 1 for all but a single site suggesting that the differences between sites were not explained well by the examined patient and registry site characteristics. The registry site number does not correspond with the order of listing of registry sites in the Additional file 1
See this image and copyright information in PMC

Comment in

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